4-Methylmorpholine → 2-Chloro-N-[1-[(3-methyl-1,2,4-oxadiazol-5-yl)methyl]-2-oxo-1,2,3,4-tetrahydroquinolin-3-yl]-6H-thieno[2,3-b]pyrrole-5-carboxamide

HRID 1178423Notes

Reaction equation

HRID 1178423 reaction equation
CN1CCOCC1.ClC(OCC)=O.[C:14]([CH2:17][N:18]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH2:21][CH:20]([NH:28][C:29]([C:31]2[NH:35][C:34]3[S:36][C:37]([Cl:39])=[CH:38][C:33]=3[CH:32]=2)=[O:30])[C:19]1=[O:40])([OH:16])=O.O[N:42]=[C:43]([NH2:45])[CH3:44]>C1COCC1.CO.C(Cl)Cl>[Cl:39][C:37]1[S:36][C:34]2[NH:35][C:31]([C:29]([NH:28][CH:20]3[CH2:21][C:22]4[C:27](=[CH:26][CH:25]=[CH:24][CH:23]=4)[N:18]([CH2:17][C:14]4[O:16][N:45]=[C:43]([CH3:44])[N:42]=4)[C:19]3=[O:40])=[O:30])=[CH:32][C:33]=2[CH:38]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 10928Ethyl chloroformateHCID 30926N-HydroxyacetamidineHCID 10319016N-[1-(Carboxymethyl)-2-oxo-1,2,3,4-tetrahydroquinolin-3-yl]-2-chloro-6H-thieno[2,3-b]pyrrole-5-carboxamide

Product 1

HCID 102527692-Chloro-N-[1-[(3-methyl-1,2,4-oxadiazol-5-yl)methyl]-2-oxo-1,2,3,4-tetrahydroquinolin-3-yl]-6H-thieno[2,3-b]pyrrole-5-carboxamideYield 61.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

N-Methylmorpholine (118 μL, 1.07 mmol) then ethyl chloroformate (103 μL, 1.07 mmol) were added to N-[1-(carboxymethyl)-2-oxo-1,2,3,4-tetrahydroquinolin-3-yl]-2-chloro-6H-thieno[2,3-b]pyrrole-5-carboxamide (Example 2; 431 mg, 1.07 mmol) in anhydrous THF (10 mL) at 0° C. After 20 minutes N′-hydroxyethanimidamide (119 mg, 1.61 mmol) was added and the reaction stirred at ambient temperature for 3 days then at reflux for 5 hours. After evaporation to dryness the residue was suspended in 1,4-dioxane and refluxed for 18 hours. On cooling the mixture was diluted with EtOAc (100 mL) and washed with H2O (25 mL). The aqueous was extracted with DCM (3×50 mL) and the combined organics dried (MgSO4), filtered and evaporated. The residue was purified by column chromatography (DCM to DCM:MeOH (9:1)) to give a yellow solid which was dissolved in MeOH:DCM (1:4) (100 mL) and shaken with macroporous silicate-carbonate scavenger resin (300 mg). Filtration then evaporation gave the title compound (291 mg, 61%) as an off-white solid.

Workup

  1. temperatureat reflux for 5 hours
  2. customAfter evaporation to dryness the residue
  3. temperaturerefluxed for 18 hours
  4. temperatureOn cooling the mixture
  5. additionwas diluted with EtOAc (100 mL)
  6. washwashed with H2O (25 mL)
  7. extractionThe aqueous was extracted with DCM (3×50 mL)
  8. dry with materialthe combined organics dried (MgSO4)
  9. filtrationfiltered
  10. customevaporated
  11. customThe residue was purified by column chromatography (DCM to DCM:MeOH (9:1))
  12. customto give a yellow solid which
  13. stirringshaken with macroporous silicate-carbonate scavenger resin (300 mg)
  14. filtrationFiltration
  15. customevaporation

Sources & evidence

ORD record
ord-f6b1c1dc8a104232a7768218893e44cb
Source dataset
uspto-grants-2007_10
Patent number
US07276517B2

Reaction notes

Loading…